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The interaction between TRIB3 and SQSTM1: a new target for the treatment of liver fibrosis

Time:2019-7-26 Source:State Key Laboratory of Bioactive Substance and Function of Natural Medicines Read:253

 

An article published online in Autophagy on July, 9 2019 identifies a new target for the treatment of liver fibrosis. The study, led by Prof. Zhuo-Wei Hu in the State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, reports that disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation.

The study reveals that the autophagy impairment mediated by the interaction between TRIB3 (tribbles pseudokinase 3) and SQSTM1 not only suppressed autophagic degradation of late endosomes but also promoted hepatocellular secretion of INHBA-enriched exosomes which caused migration, proliferation and activation of hepatic stellate cells (HSCs), the effector cells of liver fibrosis. Disrupting the TRIB3-SQSTM1 interaction with a specific helical peptide exerted potent protective effects against hepatic fibrosis by restoring autophagic flux in hepatocytes and HSCs. This study focuses on the key linking role and mechanism of TRIB3 between autophagy dysfunction and liver fibrosis, and provides a new therapeutic strategy and lead peptides for the treatment of liver fibrosis.

 

 

The interaction between TRIB3 and SQSTM1 in hepatocytes inhibits the autophagic degradation of the endosome (MVB) and promotes the release of INHBA-enriched exosomes which induce the activation of HSCs as well as the pathogenesis of liver fibrosis.

 

This work was supported by grants from the National Natural Science Foundation of China and Chinese Academy of Medical Sciences (CAMS) Innovation Found for Medical Sciences (2016-I2M-1-007; 2016-I2M-1-010; 2016-I2M-3-008). Prof. Hu Zhuo-Wei Hu is the corresponding author. Both Associate Prof. Xiao-Wei Zhang and PhD candidate Ji-Chao Zhou are the co-first authors.

 

Full text link: https://www.tandfonline.com/doi/full/10.1080/15548627.2019.1635383

 

 

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